Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China.
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jun 8;84(Pt A):71-78. doi: 10.1016/j.pnpbp.2018.01.020. Epub 2018 Feb 1.
Olanzapine (OLZ) is efficacious whereas leads to adverse metabolic effects thus lead to higher risk of cardiovascular diseases (CVD) on schizophrenia. Cytokines have been found associated with metabolic disorders. Therefore, pretreatment prediction of OLZ-induced adverse metabolic effects is urgently needed. To investigate if baseline cytokine levels could become biomarkers for pathogenesis of schizophrenia or prediction for OLZ-induced adverse metabolic effects, we recruited 75 participants, including 23 schizophrenia inpatients, who were antipsychotic-free over the past 6 months or first episode and drug-naive and 52 matched health controls, in our prospective cohort study and cross-sectional study. We simultaneously examined 7 serum cytokine levels (IFN-γ, IL-1ra, IL-1β, IL-8, TNF-α, MCP-1, VEGF) before OLZ treatment by using liquid suspension array technique and obtained clinical correlates at 4-week intervals in total 8 weeks. The psychopathology was assessed with the Positive and Negative Symptom Scale (PANSS). The metabolic parameters were BMI, TG, total cholesterol, LDL, HDL, ApoA1, ApoB, lipoprotein a, fasting glucose, HbA1c, insulin, and leptin. At baseline, IL-1ra and MCP-1 levels in schizophrenia were significantly higher than health controls (t = 4.55, P = 0.0001, t = 3.08 P = 0.003). BMI, fasting insulin, cholesterol, triglyceride, LDL, ApoB and leptin were significantly increased in patients with schizophrenia after 8 weeks of olanzapine treatment. Correlation analysis showed that the baseline IL-1ra level were significantly correlated with the increased levels of cholesterol (P = 0.004), LDL (P = 0.005), ApoB (P = 0.018) and leptin (P = 0.010), but not with the increased BMI, insulin or triglycerides. Further stepwise multiple linear regression analysis indicated that IL-1ra levels prior to treatment remained significantly associated with increased levels of cholesterol, LDL, ApoB and leptin. Above all, higher IL-1ra and MCP-1 levels may be biomarkers indicating pathogenesis of schizophrenia. Higher serum levels of IL-1ra may predict subsequent higher possibility of hypercholesterolemia and hyperleptinemia following OLZ treatment in schizophrenia patients.
奥氮平（OLZ）有效，但会导致不良代谢效应，从而增加患心血管疾病（CVD）的风险。细胞因子与代谢紊乱有关。因此，迫切需要预测 OLZ 诱导的不良代谢作用的预处理。为了研究基线细胞因子水平是否可以成为精神分裂症发病机制的生物标志物或预测 OLZ 诱导的不良代谢作用，我们在前瞻性队列研究和横断面研究中招募了 75 名参与者，包括 23 名抗精神病药物治疗的精神分裂症住院患者，他们在过去 6 个月或首次发作和药物治疗中没有使用抗精神病药物，以及 52 名匹配的健康对照者。我们同时使用液滴悬浮阵列技术在 OLZ 治疗前检测了 7 种血清细胞因子水平（IFN-γ、IL-1ra、IL-1β、IL-8、TNF-α、MCP-1、VEGF），并在总共 8 周的 4 周间隔内获得了临床相关性。使用阳性和阴性症状量表（PANSS）评估精神病理学。代谢参数包括 BMI、TG、总胆固醇、LDL、HDL、ApoA1、ApoB、脂蛋白 a、空腹血糖、HbA1c、胰岛素和瘦素。在基线时，精神分裂症患者的 IL-1ra 和 MCP-1 水平明显高于健康对照组（t=4.55，P=0.0001，t=3.08，P=0.003）。奥氮平治疗 8 周后，精神分裂症患者的 BMI、空腹胰岛素、胆固醇、甘油三酯、LDL、ApoB 和瘦素明显升高。相关分析表明，IL-1ra 水平与胆固醇（P=0.004）、LDL（P=0.005）、ApoB（P=0.018）和瘦素（P=0.010）的升高水平显著相关，但与 BMI、胰岛素或甘油三酯的升高水平无关。进一步的逐步多元线性回归分析表明，治疗前的 IL-1ra 水平与胆固醇、LDL、ApoB 和瘦素的升高水平仍显著相关。综上所述，较高的 IL-1ra 和 MCP-1 水平可能是精神分裂症发病机制的生物标志物。精神分裂症患者治疗前较高的血清 IL-1ra 水平可能预示着奥氮平治疗后出现高胆固醇血症和高瘦素血症的可能性更高。
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